On this page
CERS3
ceramide synthase 3
The CERS3 gene provides instructions for making ceramide synthase 3, an enzyme crucial for producing ceramides predominantly in the skin, which are vital for maintaining the skin's barrier function. CERS3 is essential for the synthesis of specific very long chain ceramides that are highly abundant in the stratum corneum, the outermost layer of the skin.
CERS3 is located on the long (q) arm of chromosome 15, at band 15q26.3. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 15 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The CERS3 gene, or ceramide synthase 3, plays a critical role in the synthesis of ceramides, which are a class of lipid molecules. These ceramides are particularly important in the skin, where they contribute significantly to the structural integrity and barrier function of the epidermis. Defects in CERS3 can lead to issues with skin hydration and protection, resulting in various dermatological conditions.
What the gene does
The CERS3 gene encodes an enzyme known as ceramide synthase 3. This enzyme is responsible for catalysing the N-acylation of sphingoid bases with specific fatty acyl-CoAs to form ceramides. Ceramide synthase 3 primarily produces very long chain and ultra long chain ceramides, which are highly enriched in the stratum corneum of the skin. These particular ceramides are crucial for forming the lipid lamellae that act as the skin's permeability barrier, preventing water loss and protecting against environmental insults. Proper function of CERS3 is therefore fundamental for maintaining skin hydration and overall skin health.
Video: Genetics 101
Chromosome location
The CERS3 gene is situated on chromosome 15 at position 15q26.3. This specific genomic location indicates its precise position within the human genome. The gene's location helps in understanding its inheritance patterns and its relationship to other genes on the chromosome.
Protein structure
The CERS3 protein consists of 383 amino acids. It features several distinct regions and domains crucial for its enzymatic activity. A Homeobox-like region spans amino acids 66-127, suggesting potential regulatory or structural roles. A prominent TLC domain, located between amino acids 130 and 331, is likely integral to the protein's ceramide synthase function. Additionally, a Disordered region is identified from amino acids 342-363, which may afford flexibility or mediate interactions with other molecules.
Key variants
Genetic variations within the CERS3 gene can impact the structure and function of the ceramide synthase 3 enzyme. These variants include changes such as single nucleotide polymorphisms, insertions, or deletions that may alter the protein's ability to synthesise ceramides effectively. The nature and location of these variants dictate their potential effect on protein function and associated health consequences.
Sample of pathogenic variants
9 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.363del | p.Asn122fs | Pathogenic | ★☆☆☆ | not provided |
c.43T>A | p.Trp15Arg | Pathogenic | ★☆☆☆ | not provided |
c.540G>A | p.Trp180Ter | Pathogenic | ★☆☆☆ | Autosomal recessive congenital ichthyosis 9 |
c.662del | p.Phe221fs | Pathogenic | ★☆☆☆ | not provided |
c.685C>T | p.Arg229Cys | Pathogenic | ★☆☆☆ | Lamellar ichthyosis |
c.686G>A | p.Arg229His | Pathogenic | ★☆☆☆ | Lamellar ichthyosis |
c.731G>A | p.Trp244Ter | Pathogenic | ★☆☆☆ | Autosomal recessive congenital ichthyosis 9 |
GRCh37/hg19 15q26.3(chr15:101061066-101081879)x1 | - | Pathogenic | - | not provided |
c.43T>C | p.Trp15Arg | Pathogenic | - | Autosomal recessive congenital ichthyosis 9 |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the CERS3 gene are associated with inherited skin disorders, most notably certain forms of ichthyosis. These conditions typically manifest with dry, scaly skin due to a compromised skin barrier. The specific inheritance pattern for CERS3-related conditions can vary, indicating different genetic mechanisms potentially leading to similar clinical presentations.
No disease links recorded for this gene in our reference set.
UK clinical status
CERS3 gene testing is included on several NHS Genomic Medicine Service panels, indicating its clinical relevance within the UK. It is part of the 'Autosomal recessive congenital ichthyosis', 'Foetal anomalies (R21)', 'Ichthyosis and erythrokeratoderma (R165)', and 'Palmoplantar keratodermas (R166)' green panels. This inclusion facilitates genetic diagnosis and management for individuals with related conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the CERS3 gene?
The CERS3 gene produces ceramide synthase 3, an enzyme essential for synthesising very long chain ceramides. These ceramides are crucial for maintaining the skin's barrier function, preventing water loss, and protecting against environmental factors.
Which conditions are associated with variants in the CERS3 gene?
Variants in the CERS3 gene are primarily associated with inherited skin disorders, particularly certain types of ichthyosis, which are characterised by dry, scaly skin resulting from a compromised skin barrier.
How does CERS3 relate to skin health?
CERS3 is vital for skin health because it enables the production of specific ceramides that are major components of the skin's outer layer, the stratum corneum. These ceramides form a protective barrier that regulates skin hydration and protects against external damage.